Case Western Reserve researchers have identified a genetic factor that blocks the blood vessel inflammation that can lead to heart attacks, strokes, and other potentially life-threatening events. The breakthrough involving Kruppel-like factor (KLF) 15 is the latest in a string of discoveries from the laboratory of professor of medicine Mukesh K. Jain, M.D., F.A.H.A., that involves a remarkable genetic family. Kruppel-like factors appear to play prominent roles in everything from cardiac health and obesity to metabolism and childhood muscular dystrophy. School of Medicine instructor Yuan Lu, M.D., a member of Dr. Jain’s team, led the study involving KLF-15 and its role in inflammation, which was published online on Sepember 3, 2013 in the Journal of Clinical Investigation. Dr. Lu and colleagues observed that KLF-15 blocks the function of a molecule called NF-kB, a dominant factor responsible for triggering inflammation. This finding reveals a new understanding of the origins of inflammation in vascular diseases, and may eventually lead to new, targeted treatment options. “It had been suspected that smooth muscle cells were related to inflammation, but it hadn’t been pinpointed and specifically linked to disease,” said Dr. Jain, Ellery Sedgwick Jr. Chair and director, Case Cardiovascular Research Institute at Case Western Reserve School of Medicine. Dr. Jain also is chief research officer for the Harrington Heart & Vascular Institute at University Hospitals Case Medical Center. “This work provides cogent evidence that smooth muscle cells can initiate inflammation and thereby promote the development of vascular disease.” Smooth muscle cells are only one of two major cell types within blood vessels walls. The other cell type, endothelium, has traditionally taken the blame for inflammation, but Dr.

Biologists at the University of California (UC), San Diego, have identified a new component of the cellular mechanism by which humans and animals automatically check the quality of their nerve cells to assure they’re working properly during development. In a paper published in the September 4, 2013 issue of the journal Neuron, the scientists report the discovery in the laboratory roundworm C. elegans of a “quality check” system for neurons that uses two proteins to squelch the signals from defective neurons and marks them for either repair or destruction. “To be able to see, talk, and walk, nerve cells in our body need to communicate with their right partner cells,” explains Dr. Zhiping Wang, the lead author in the team of researchers headed by Dr. Yishi Jin, a professor of neurobiology in UC San Diego’s Division of Biological Sciences and a professor of cellular and molecular medicine in its School of Medicine. “The communication is mediated by long fibers emitting from neurons called axons, which transmit electric and chemical signals from one cell to the other, just like cables connecting computers in a local wired network. In developing neurons, the journey of axons to their target cells is guided by a set of signals. These signals are detected by ‘mini-receivers’—proteins called guidance receptors—on axons and translated into ‘proceed,’ ‘stop,’ ‘turn left’ or ‘turn right.’ Thus, the quality of these receivers is very important for the axons to interpret the guiding signals.” Dr. Jin, who is also an Investigator of the Howard Hughes Medical Institute, says defective protein products and environmental stress, such as hyperthermia, can sometimes jeopardize the health and development of cells. “This may be one reason why pregnant women are advised by doctors to avoid saunas and hot tubs,” she adds.

A team led by scientists from The Scripps Research Institute (TSRI) has shown that a protein once thought to inhibit the growth of tumors is instead required for initial tumor growth. The findings could point to a new approach to cancer treatment. The study was published as the cover article of the September 3, 2013 issue of the journal Science Signaling. The focus of the study was angiomotin, a protein that coordinates cell migration, especially during the start of new blood vessel growth and proliferation of other cell types. “We were the first to describe angiomotin’s involvement in cancer,” said Dr. Joseph Kissil, a TSRI associate professor who led the studies. “ And while some following studies found it to be inhibiting, we wanted to clarify its role by using both cell studies and animal models. As a result, we have now found that it is not an inhibitor at all, but instead is required for Yap to produce new tumor growth.” Yap (yes-associated-protein) is a potent oncogene that is over-expressed in several types of tumors. In addition to identifying angiomotin’s critical role in tumor formation, Dr. Kissil and his colleagues found the protein is active within the cell nucleus. Earlier cell studies focused on the function of the protein at the cell membrane. “This pathway, which was discovered less than a decade ago, appears to regulate processes that are closely linked to cancer,” Dr. Kissil said. “The more we study it, the more we see its involvement.” The first authors of the study are Dr. Chunling Yi of Georgetown University Medical Center and Dr. Zhewei Shen of the University of Pennsylvania. Other authors include Dr. Anat Stemmer-Rachamimov of Massachusetts General Hospital; Drs. Noor Dawany, Louise C. Showe and Qin Liu of The Wistar Institute; Dr. Scott Troutman of TSRI; Dr. Akihiko Shimono of TransGenic, Inc.; Dr.

A new systematic review published online on August 9, 2013 in the British Journal of Nutrition, is one of the first to focus on patterns of vitamin D status worldwide and in key population subgroups, using continuous values for 25(OH)D to improve comparisons. Principal investigator, Dr. Kristina Hoffmann of the Mannheim Institute of Public Health (MIPH), Medical Faculty Mannheim, Heidelberg University, stated, “The strength of our study is that we used strict inclusion criteria to filter and compare data, using consistent values for 25(OH)D. Although we found a high degree of variability among reports of vitamin D status at the population level, more than one-third of the studies reviewed reported mean serum 25(OH)D values below 50 nmol/L.” Low levels of vitamin D have a potentially serious impact on health, particularly on bone and muscle health. In children, vitamin D deficiency is a cause of rickets; while in adults low values are associated with osteomalacia, osteopenia, osteoporosis, and risk of fracture. Emerging evidence also points to increased risk for cancer and cardiovascular diseases. Yet despite its importance to public health, data about vitamin D status at the population level are limited and studies are hampered by lack of consensus and consistency.

A team of researchers in Ireland, together with collaborators, has found evidence that altering the chemistry of an electrode surface (surface engineering) can help microbial communities to connect to the electrode to produce more electricity (electron-exchange) more rapidly compared to unmodified electrodes. The work was published online on August 8, 2013 in RSC Advances. Electron exchange is at the heart of all redox reactions occurring in the natural world, as well as in bioengineered systems: so called “biolectrochemical systems.” Practical applications of these systems include current generation, wastewater treatment, and biochemical and biofuel production. The microbial-electrode interface is a sum of complex physical-chemical and biological interactions permitting microbes to exchange electrons with solid electrodes to produce bioelectrochemical systems. In these systems, the microbes, compete, and self-select electrode materials for electron exchange capabilities. However, to date this selection is not well understood yet electricity or chemicals can be produced using various substrates, including wastewater or waste gases, depending upon operational settings, says Dr. Amit Kumar, who worked under the leadership of Dr. Dónal Leech at the National University of Ireland Galway in Ireland. The Biomolecular Electronics Research Laboratory has been working on probing conditions for selection of electrodes by microbes for several years, and has recently adopted an approach to tailor the chemistry of electrode surfaces that will help them better understand the selection mechanism say Dr. Kumar and Dr. Leech.The group’s first result shows that surfaces modified with nitrogen-containing amines result in higher and more rapid production of current, compared to those without this modification, when placed in microbial cultures.